This application is a request for transfer of funding for project 1Ro1-AM28643-01 to the University of Florida from the USPHS Hospital following sudden closure of the latter institution on 10-30-81. The project will continue at the location without substantial change in design or methods. The purpose of this research is to investigate chronic renal regulation of systemic acid-base equilibrium in the dog as it is modulated separately and interrelatedly by (a) 1,25-dihydroxycholecalciferol 1,25-(OH)2D3, (b) plasma Ca++ concentration, (c) parathyroid hormone (PTH), and (d) urinary phosphate excretion. Numerous studies have been carried out to investigate the acute effects of disturbances in calcium, vitamin D, and PTH on plasma and urinary-acid-base composition, but whether these reported effects persist and are of sufficient magnitude to result in sustained alterations in systemic acid-base equilibrium with chronicity of the initiating disturbances requires further investigation. Furthermore, the chronic effects of alteration in systemic inorganic phosphate load in non-phosphate depleted animals have not been investigated in relation to development of the defense against metabolic acid-base disorders. The proposed studies will employ the chronic balance technique in dogs to characterize the chronic renal and systemic effects of specific, controlled alterations in each of four factors known to acutely alter renal and/or systemic acid-base equilibrium. Accordingly, chronic experimental models of 1,25-(OH)2D3, CA++, phosphate and PTH excess states as well as models of CA++, phosphate and PTH deficiency states will be examined with both paired and unpaired control of interrelated factors. These investigations will provide the first systematic investigation of the chronic renal and systemic acid-base consequences of experimental variation of the above named factors and will, in turn, increase our understanding of the pathogenesis of disturbances in acid-base metabolism in clinical disorders of primary hyperparathyroidism, hypoparathyroidism, hypocalcemia, hypercalcemia, and vitamin D intoxication, as well as the roles of dietary calcium and phosphage in the magnitude and character of these disorders.